rs200451908

Variant names:

• chr15-23440773-A-C
• rs200451908
• NM_001304388.2:c.1702T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-23440773-A-C
• chr15-23440773-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001304388.2(GOLGA6L2):​c.1702T>G​(p.Ser568Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L2 NM_001304388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.690
• Publications: 7 publications found

Genes affected

GOLGA6L2 (HGNC:26695): (golgin A6 family like 2) Predicted to be located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010241866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304388.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	NM_001304388.2	MANE Select	c.1702T>G	p.Ser568Ala	missense	Exon 8 of 8	NP_001291317.1	Q8N9W4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L2	ENST00000567107.6	TSL:5 MANE Select	c.1702T>G	p.Ser568Ala	missense	Exon 8 of 8	ENSP00000454407.1	Q8N9W4-3
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*983T>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456523.1	H3BS38
	GOLGA6L2	ENST00000566571.5	TSL:5	n.*983T>G		3_prime_UTR	Exon 7 of 7	ENSP00000456523.1	H3BS38

Frequencies

GnomAD3 genomes AF: 0.00629 AC: 226 AN: 35938 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00820

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.00728

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.000461

Gnomad MID AF: 0.0139

Gnomad NFE AF: 0.00484

Gnomad OTH AF: 0.00791

GnomAD2 exomes AF: 0.0000676 AC: 3 AN: 44378 AF XY: 0.0000773

Gnomad AFR exome AF: 0.000797

Gnomad AMR exome AF: 0.000254

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00107

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000168 AC: 21 AN: 1249250 Hom.: 0 Cov.: 48 AF XY: 0.0000210 AC XY: 13 AN XY: 619626

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000722 AC: 2 AN: 27692

American (AMR) AF: 0.000121 AC: 4 AN: 32946

Ashkenazi Jewish (ASJ) AF: 0.0000431 AC: 1 AN: 23196

East Asian (EAS) AF: 0.00 AC: 0 AN: 33316

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 73210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.0000104 AC: 10 AN: 959746

Other (OTH) AF: 0.0000571 AC: 3 AN: 52514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00628 AC: 226 AN: 35974 Hom.: 0 Cov.: 0 AF XY: 0.00525 AC XY: 91 AN XY: 17332

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0101 AC: 111 AN: 10936

American (AMR) AF: 0.00214 AC: 8 AN: 3742

Ashkenazi Jewish (ASJ) AF: 0.00728 AC: 6 AN: 824

East Asian (EAS) AF: 0.0151 AC: 14 AN: 930

South Asian (SAS) AF: 0.00478 AC: 4 AN: 836

European-Finnish (FIN) AF: 0.000461 AC: 1 AN: 2170

Middle Eastern (MID) AF: 0.0143 AC: 1 AN: 70

European-Non Finnish (NFE) AF: 0.00484 AC: 76 AN: 15710

Other (OTH) AF: 0.00586 AC: 3 AN: 512

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.315 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.7
DANN	Benign	0.71
FATHMM_MKL	Benign	0.00025	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.010	T
PhyloP100		0.69
PROVEAN	Benign	-0.010	N
Sift4G	Benign	1.0	T
Vest4		0.13
MVP		0.35
MPC		0.013
Varity_R		0.099
gMVP		0.014
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200451908; hg19: chr15-23685920; COSMIC: COSV61477950;